Treatment options for patients with hepatitis C virus (HCV) genotype 3 infection are limited, with the currently approved all-oral regimens requiring 24-week treatment and the addition of ribavirin. This phase 3 study (ALLY-3; http://www.ClinicalTrials.gov NCT02032901) evaluated the 12-week regimen of daclatasvir (pangenotypic NS5A inhibitor) plus sofosbuvir (pangenotypic NS5B inhibitor) in patients infected with genotype 3. Patients were either treatment-naive (n=101) or treatment-experienced (n=51) and received daclatasvir 60mg plus sofosbuvir 400mg once daily for 12 weeks. Co-primary endpoints were the proportions of treatment-naive and treatment-experienced patients achieving a sustained virologic response at posttreatment Week 12 (SVR12). SVR12 rates were 90% (91/101) and 86% (44/51) in treatment-naive and treatment-experienced patients, respectively; no virologic breakthrough was observed, and ≥99% of patients had a virologic response at the end of treatment. SVR12 rates were higher in patients without cirrhosis (96% [105/109]) than in those with cirrhosis (63% [20/32]). Five of 7 patients who previously failed treatment with a sofosbuvir-containing regimen and 2 of 2 patients who previously failed treatment with an alisporivir-containing regimen achieved SVR12. Baseline characteristics, including gender, age, HCV RNA levels, and IL28B genotype, did not impact virologic outcome. Daclatasvir plus sofosbuvir was well tolerated; there were no adverse events leading to discontinuation and only 1 serious adverse event on-treatment, which was unrelated to study medications. The few treatment-emergent grade 3/4 laboratory abnormalities that were observed were transient.

Conclusion: A 12-week regimen of daclatasvir plus sofosbuvir achieved SVR12in 96% of patients with genotype 3 infection without cirrhosis and was well tolerated. Additional evaluation to optimize efficacy in genotype 3-infected patients with cirrhosis is underway.